As it is known, drugs are frequently stored in powdered form (lyophilized) because they rapidly lose their power once they are mixed into a solution. Powder drugs are typically used for parenteral administration, and in common language are often referred to as “powder for injection” (PI), “dry powder injection” or “powder for reconstitution.” A wide sample list of dry powder for injection is available on the U.S. Pharmacopeia under USP 29-NF 24.
The above powdered drugs need to be mixed in a container (normally a vial) with a liquid generally referred to as “the diluents”, i.e. reconstituted.
Once the diluents has been added to the powdered drug, the liquid-powder mixture needs to be agitated in the container until the drug powder is completely dissolved, i.e. the reconstitution process is terminated. For instance the USP defines the completeness of the reconstitution process as the status when no visible residue of undissolved powder is visible or the constituted solution is not significantly less clear than an equal volume of the diluents or purified water.
For most of the chemical drugs, no special handling and technique is described for achieving an efficient reconstitution, and in most of the cases effectiveness of the reconstitution only focuses on the effectiveness of the agitation, where the optimum procedure would be achieved by the agitation of the container that completely dissolves the drug in the shortest time.
Sometimes, commercially drugs are subject to limited instructions on how to perform agitation of the container, but these instructions are often vague and generic such as “gently swirl”, or “avoid shaking.” For most of the cases, in fact, the instructions are provided to prevent foaming or gel formation in the reconstituted drug or in any case to limit overpressure in the container that could subsequently result into spray or aerosol effects when the container is opened.
More accurate instructions are normally not available, because the reconstitution process is performed by an operator, typically a pharmacy technician, handling and moving the container to be reconstituted; the result largely depends on individual skills and training of the operator and often is also conditioned by environmental constraints. In addition, when agitation needs to be carried out by an operator, no accurate agitation instructions could be implemented adequately, when reconstitution time could take from few seconds to minutes, as no operator would be in the condition to manually repeat a complex movement for such a long time.
For this reason, most of the research and solutions in the past years focused on the design of automated system for powdered drug reconstitution aiming at optimizing the agitation process, by achieving the best dissolution of the powdered drug in the shortest time.
Even though several automated systems for powdered drug reconstitution have been designed and are currently available on the market, only a limited number of degrees of freedom has been utilized so far to perform the agitation.
Systems available on the market perform the agitation by the following movements:                rotating the container around its longitudinal axis;        rotate the container vial around a central axis of a rotating disk where the container has their longitudinal axis parallel or inclined or even orthogonal to such rotation axis;        shaking container with variable frequency;        agitating the container through a roto-translational movement around two or three axes; and        inducing a vortex within the diluents by means of a mixing tool immersed in the diluents.        
None of the current system is suitable for the implementation of a complex agitation technique based on a combination of more than one movement, for example rotating the container around a vertical axis, then moving the longitudinal axis of the container on the surface of a cone and then gently shaking the container with close to zero velocity at the level of the vial stopper, and larger velocity at the bottom of the stopper.
A method for the reduced, controlled and repeatable reconstitution method for the effective dissolution of a powder drug is therefore needed here.